Investigations will continue to be directed at the hepatic actions and interactions of polychlorinated compounds, particularly mirex, dieldrin, hexachlorobenzene and polychlorinated biphenyls, under conditions of long-term low-level exposure of mice, rats and monkeys. Special attention will be paid to the relationship between the observed enlargement of the liver and development of liver nodules on the one hand, and on the other the pharmacokinetics and biotransformation of these compounds, their tissue levels and states of binding. The effects of simultaneous administration of two or more of these compounds will be studied further, in relation to the role of involvement of subcellular organelles, including lysosomes, in the resulting hepatotoxic interactions. Further attention will be given to the altered state of the intestinal epithalium and reticuloendothelial system resulting from uptake and retention of carrageenans and other polyanionic macromolecular compounds, with a view to elucidating the mechanisms of ulceration and of squamous metaplasia seen in different species. The effects of dietary factors on the actions of polyanionic compounds will be explored, and the consequences of toxicological interaction of such compounds with simultaneous exposure to environmental pollutants,including intestinal carcinogens, will be examined further. Studies on the mechanisms of action of methylmercury in brain and kidney will be continued and extended to encompass interactions with lead, cadmium and other environmental contaminants.